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Biomedical subjects

H Asada

Publications and source records attributed to H Asada.

At least 19 recordsLinked to original sources
PubMed2006

Transthoracic direct current shock facilitates intramyocardial transfection of naked plasmid DNA infused via coronary vessels in canines.

Catheter-mediated, percutaneous, transluminal delivery of naked plasmid DNA (pDNA) into myocardium may offer a valuable strategy to heart diseases. Here, we examined whether clinically available transthoracic direct current (DC) shock improves intracoronary naked DNA transfection into myocardium. Plasmid vector encoding the GL3 luciferase was infused retrogradely into the coronary veins of beagle dogs, whereas another pDNA solution was infused into the left coronary artery. During and after these procedures, the coronary venous sinus was occluded by balloon, and transthoracic DC shock of 200 J was applied immediately after the infusions. Without DC shock, no remarkable increase in luciferase activity was demonstrated in any part of the left ventricular myocardium. In the presence of DC pulsation, significant luciferase expression was detected in the regions that were supplied by left anterior descending coronary artery (LAD), whereas the gene expression in the right coronary artery (RCA) regions was much less drastic. X-gal (5-bromo-4-chloro-3-indolyl-beta-D-galactoside) staining of cardiac cross-sections also revealed regional expression of beta-galactosidase. Immunohistochemical examinations of heart cryosections revealed that cardiomyocytes in LAD regions successfully expressed transgene product. The present system may enable a new strategy for myocardial gene therapy, without any special device or technique other than cardiac catheterization and DC cardioversion that are generally performed in ordinary hospitals.

Animals↗
PubMed2005

Cytokine genetic adjuvant facilitates prophylactic intravascular DNA vaccine against acute and latent herpes simplex virus infection in mice.

Intravascular plasmid DNA (pDNA) vaccine encoding herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) effectively induces prophylactic immunity against lethal HSV-1 infection in mice. We investigated whether the vaccine potency is further improved by coadministration of cytokine genes together with a low dose of genetic vaccine. pDNA encoding IL-12, IL-15, IL-18 or IL-21 was capable of elevating survival rates of HSV-1-infected mice when coinjected with 1 microg of gB pDNA, while IL-10 gene delivery failed to affect the effectiveness of the genetic immunization. Although only 17% of mice survived acute HSV infection after the gB pDNA vaccination at a dose of 1 microg, all mice coadministered with 1 microg each of gB and IL-12 pDNAs not only survived the acute infection but also escaped latent infection. In these animals, the neutralizing antibody against HSV-1 was abundantly produced, and CTL activity against the gB antigen was augmented. Coadministration of the gB and IL-12 genes also elevated the serum level of interferon-gamma. Adaptive transfer experiments indicated that soluble factors contributed to preventive immunity, while cell components alone were not capable of protecting mice from fatal viral infection. These results strongly suggest potential usefulness of Th1 cytokine genes as effective molecular adjuvants that facilitate specific humoral as well as cellular immune responses elicited by intravascular molecular vaccination.

Acute Disease↗
PubMed2004

Autoimmune thyroid disease in anti-Ro/SS-A-positive children with annular erythema: report of two cases.

Anti-Ro/SS-A-associated recurrent annular erythema is a rare disorder, and represents a cutaneous manifestation of primary Sjögren's syndrome (SS). We report two childhood cases complicated with autoimmune thyroid disease, one with Graves' disease and the other with autoimmune thyroiditis. Both children were positive for anti-Ro/SS-A and anti-La/SS-B antibodies. One patient was lacking clinical SS with objective evidence of salivary gland involvement, while the other was diagnosed with primary SS. Our observation suggests that autoimmune thyroid disease in the subset of anti-Ro/SS-A-positive children with annular erythema might occur with similar frequency to that in adult primary SS.

Adolescent↗
PubMed2004

Venous blood flow through vein grafts before harvesting minimizes endothelial cell desquamation immediately after implantation.

AIM: The aim of this paper was to examine effectiveness of maintaining venous blood flow through dissected, but not harvested, grafts on prostaglandin I2 production and endothelial cell regeneration after implantation. METHODS: Using 10 dogs, 8-cm-long bilateral jugular veins were dissected; 1 was harvested, and immersed in heparinized blood for 60 or 120 min. The other was left in situ with retained blood flow until harvest after 60 or 120 min. Two 1-cm-long specimens were obtained from these 4 graft types and subjected to PGI2 assay or silver nitrate staining for measurement of endothelial cell coverage area. The remaining 6-cm portions of the 120-min grafts were autogenously implanted into the abdominal aorta, retrieved after 7 days and assayed and measured. RESULTS: Comparisons between groups suggested beneficial effects of preserving venous blood flow until implantation on endothelial coverage and PGI2 production (p<0.05). CONCLUSION: Venous blood flow through dissected vein grafts effectively helps preserve PGI2 production.

Animals↗
PubMed2003

Gamma knife radiosurgery for metastatic tumours in the brain stem.

BACKGROUND: Stereotactic radiosurgery has become important in the treatment of metastatic brain tumours and is often the first choice modality for eloquent or deep locations such as the brain stem. This study evaluated the efficacy of gamma knife radiosurgery (GKS) for the treatment of brain stem metastases. METHODS: The medical records of 25 patients with 31 tumours, 11 men and 14 women aged 42 to 78 years (mean 57.1 years), who underwent GKS for metastatic tumours in the brain stem were retrospectively reviewed. The results of GKS were evaluated according to the change in tumour size on neuro-imaging. FINDINGS: The most common location of the primary malignancy was the lung followed by the breast. Adenocarcinoma was found in 19 patients (24 lesions). No case of squamous cell carcinoma was found. The mean calculated tumour volume was 2.1 cm(3) and the mean prescription dose to the tumour margin was 13.0 Gy. Mean duration of neuro-imaging follow up was 5.2 months and the overall tumour control rate was 77.4%. There was a significant correlation between the marginal dose delivered and the effect on neuro-imaging. New radiation-induced injury in the surrounding brain occurred in only 2 patients. INTERPRETATION: GKS for brain stem metastases using a marginal dose of 15 Gy or less is effective and relatively safe. Accurate targeting of the tumour and safe dose planning are essential to obtain satisfactory results with GKS for brain stem metastases.

Adenocarcinoma↗
PubMed2003

Nonviral genetic transfer of Fas ligand induced significant growth suppression and apoptotic tumor cell death in prostate cancer in vivo.

To accomplish efficient nonviral gene therapy against prostate cancer (PC), Epstein-Barr virus (EBV)-based plasmid vectors containing EBNA1 gene and oriP were employed and combined with a cationic polymer or cationic lipid. When EBV-plasmid/poly-amidoamine dendrimer complex was injected into PC-3-derived tumors established in severe combined immunodeficiency mice, a considerable expression of marker gene was obtained in the tumors, and the expression level was more than eight-fold higher than that achieved by conventional plasmid vector/dendrimer. Since most PC cells express the apoptotic signal molecule Fas (Apo-1/CD95) on their surface, Fas ligand (FasL) gene was transferred into PC cells to kill the tumor cells. In vitro transfection with pGEG.FasL (an EBV-plasmid with the FasL gene) significantly reduced the viability of PC cells, which subsequently underwent apoptosis. Intratumoral injections of pGEG.FasL into PC induced significant growth suppression of the xenograft tumors, in which typical characteristics of apoptosis were demonstrated by TUNEL staining and electron microscopic observations. When pGEG.FasL transfer was accompanied by systemic administrations of cisplatin, the tumors were inhibited even more remarkably, leading to prolonged survival of the animals. FasL gene transfection by means of EBV-based plasmid/cationic macromolecule complexes may provide a practical therapeutic strategy against PC.

Antineoplastic Agents↗
PubMed2003

Intravascular naked DNA vaccine encoding glycoprotein B induces protective humoral and cellular immunity against herpes simplex virus type 1 infection in mice.

Naked plasmid DNA (pDNA) vaccine expressing herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) was tested for protective activity against acute HSV-1 infection in mice. The pDNA was intravenously injected into Balb/c mice via their tail vein under high pressure, and the vaccination was performed two times at an interval of 7 days. The gB gene vaccination significantly protected the mice from subsequent intraperitoneal challenge with a lethal dose of HSV-1, which killed all the animals given control plasmid or saline. The protective activity was correlated with the dose of the plasmid inoculated, the survival rate reaching 83% in mice vaccinated with 5 microg of pDNA. The vaccinated mice were also protected from latent HSV infection. The immunized mice showed significant elevation in neutralizing antibody against HSV-1 as well as serum levels of interleukin-12 (IL-12) and interferon-gamma (IFN-gamma). When mice were immunized with 5 microg of an Epstein-Barr virus (EBV)-based plasmid vector harboring the gB, the cytotoxic T lymphocytes (CTLs) activity and proliferative response for HSV-1 were also induced. The results strongly suggest that intravenous immunization of naked pDNA may induce humoral and cellular immune responses against the virus, leading to a significant prophylactic outcome against HSV-1 infection in mice.

Animals↗
PubMed2003

[Adhesion or organization during surgery due to mediastinoscopy before induction therapy for non-small cell lung cancer].

We conducted a retrospective study to investigate amounts of adhesion or organization during surgery due to mediastinoscopy before induction therapy for non-small cell lung cancer (NSCLC). A case series of 13 patients (c-stage IIIA in 11 and IIIB in 2) with right-side NSCLC who underwent induction therapy were assessed. They were between 39 and 71 years old and 8 males and 5 females. Induction therapy was chemotherapy alone in 4 cases and chemo-radiotherapy in 9 cases. The mediastinocopy was used in 4 cases. Mediastinal lymph node resection was incomplete in 3 of the 4 (75%) cases among the mediastinoscopy group but the no-mediastioscopy group had no incomplete resection (p = 0.01), though 2 of the 9 (22%) cases among the chemo-radiation group and 1 of the 4 (25%) among the chemo alone group (p > 0.9). Severe adhesion or organization can occur after the mediastinoscopy and induction therapy, which might be a course of incomplete mediastinal lymph node resection.

Adult↗
PubMed2002

Fetal gastric size in normal and abnormal pregnancies.

OBJECTIVE: The aim of this observational study was to construct an ultrasound index of fetal gastric size for the prenatal detection of congenital digestive tract obstruction. SUBJECTS: A total of 386 fetal measurements were performed in routine ultrasonographic examinations of women with normal singleton pregnancies between 18 and 39 weeks of gestation. Gastric measurements were also performed in 13 fetuses with digestive tract obstruction. METHODS: The ultrasound plane which included the pylorus and which provided the largest stomach area was used for definition and measurement of gastric area and maximal longitudinal dimension. The transverse section at the center of the gastric corpus was used for transverse and anteroposterior dimensions. Gastric volumes were calculated as a prolate ellipsoid. The gastric area ratio was defined as the gastric area divided by the transverse abdominal area. Biparietal diameter (BPD) and abdominal transverse area were also measured. RESULTS: The fetal gastric area was significantly correlated with fetal gastric volume (r = 0.91) and gestational age (r = 0.74). However, the correlation coefficient for gastric area with gestational age was smaller than those of the BPD (r = 0.97) with gestational age and abdominal transverse area with gestational age (r = 0.97). Gastric area ratio decreased slightly towards term. The gastric area ratio was below the 95% confidence intervals for the predicted values in all five fetuses with esophageal atresia, and exceeded the 95% confidence intervals in seven of the eight fetuses with duodenal atresia or intestinal tract obstruction. CONCLUSION: Fetal gastric area correlates with ultrasound-determined gastric volume measurements and appears to be useful in the assessment of digestive tract anomalies.

Case-Control Studies↗
PubMed2002

Proliferating cell nuclear antigen positive cells in the hippocampal subgranular zone decline after irradiation in a rodent model.

Four-week-old ICR mice were systemically exposed to 18Gy X-rays. Afterwards, the expression of proliferating cell nuclear antigen (PCNA) in the cerebrum was observed with time using Western blot analysis and immunohistochemical staining. As a result, PCNA-positive cells were observed in the subgranular zone (SGZ) of the hippocampus and subventricular zone (SVZ) of the lateral ventricles in unirradiated mice. The number of PCNA-positive cells decreased with time in all zones after irradiation, but the decrease was more marked in the hippocampal SGZ. We think that PCNA-positive cells are stem cells. The selective vulnerability to radiation in the hippocampus is considered to be attributed to the fact that stem cells in the SGZ selectively undergo radiation-induced apoptosis.

Animals↗
PubMed2001

Identification of anti-herpes simplex virus antibody-producing B cells in a patient with an atypical RAG1 immunodeficiency.

Mutations of the RAG1 or RAG2 protein that eliminate their recombination activity result in T-B-severe combined immunodeficiency (SCID), whereas mutations retaining partial recombination activity lead to Omenn syndrome, a peculiar SCID characterized by increased host T cells and absence of circulating B cells. The prognosis of this disease is fatal, unless hematopoietic stem cell transplantation is performed. This study reports a case of atypical SCID, carrying RAG1 mutations. The patient survived for 6 years without hematopoietic stem cell transplantation. The missense mutation, tested by in vivo recombination assay, revealed residual recombination activity. By the age of 5 years, the patient developed host B cells, but not T cells, possibly due to engrafted maternal T cells. In addition, the host B cells were able to produce antibodies, including anti-herpes simplex virus-antibodies. The fact that host B cells could produce antibodies in this patient could explain not only the mild phenotype observed but also, at least in part, how patients with Omenn syndrome produce immunoglobulin E and sometimes immunoglobulin M, as the same missense mutation of RAG1 gene has been reported in a patient with Omenn syndrome.

Adult↗
PubMed2001

Stable operation of a 300-m laser interferometer with sufficient sensitivity to detect gravitational-wave events within our galaxy.

TAMA300, an interferometric gravitational-wave detector with 300-m baseline length, has been developed and operated with sufficient sensitivity to detect gravitational-wave events within our galaxy and sufficient stability for observations; the interferometer was operated for over 10 hours stably and continuously. With a strain-equivalent noise level of h approximately 5x10(-21)/sqrt[Hz], a signal-to-noise ratio of 30 is expected for gravitational waves generated by a coalescence of 1.4M-1.4M binary neutron stars at 10 kpc distance. We evaluated the stability of the detector sensitivity with a 2-week data-taking run, collecting 160 hours of data to be analyzed in the search for gravitational waves.

Astronomy↗
PubMed2001

Glutamate synthesis via photoreduction of NADP+ by photostable chlorophyllide coupled with polyethylene-glycol.

Chlorophyllide a was coupled with alpha-(3-aminopropyl)-omega-methoxypoly(oxyethylene) (PEG-NH2) to form a PEG-chlorophyllide conjugate through an acid-amide bond. The conjugate catalyzed the reduction of methylviologen in the presence of 2-mercaptoethanol. It also catalyzed the photoreduction of NADP+ or NAD+ in the presence of ascorbate as an electron donor and ferredoxin-NADP+ reductase as the coupling enzyme. Utilizing the reducing power of NADPH generated by PEG-chlorophyllide conjugate under illumination, glutamate was synthesized from 2-oxoglutarate and NH4+ in the presence of glutamate dehydrogenase. PEG-chlorophyllide conjugate was quite stable toward light illumination compared with chlorophyll a. The increase in the molecular weight of PEG in the PEG-chlorophyllide conjugates was accompanied by the enhancement of photostability of the conjugate and also by the increased solubility in the aqueous solution.

Carboxylic Ester Hydrolases↗